1. Field of the Invention
This invention is in the field of biologically active compounds.
2. Discussion of the Background
The prior art is replete with examples of chemically, microbially, or enzymatically synthesizing compounds with biological activity. The goal of these efforts is the discovery of new and improved pharmaceutical compounds.
The discovery of new pharmaceutical compounds is for the most part a trial and error process. So many diverse factors constitute an effective pharmaceutical compound that it is extremely difficult to reduce the discovery process to a systematic approach. Typically, thousands of organic compounds must be isolated from biological sources or chemically synthesized and tested before a pharmaceutical compound is found.
Synthesizing and testing new compounds for biological activity, which is the first step in identifying a new synthetic drug, is a time consuming and expensive undertaking. Typically, compounds must by synthesized, purified, tested and quantitatively compared to other compounds in order to identify active compounds or identify compounds with optimal activity. The synthesis of new compounds is accomplished for the most part using standard chemical methods. Such methods provide for the synthesis of virtually any type of organic compound; however, because chemical reactions are non-specific, these syntheses require numerous steps and multiple purifications before a final compound is produced and ready for testing.
New biological and chemical approaches have recently been developed which provide for the synthesis and screening of large libraries of small peptides and oligonucleotides. These methods provide for the synthesis of a broad range of chemical compounds and provide the means to potentially identify biologically active compounds. The chemistries for synthesizing such large numbers of these natural and non-naturally occurring polymeric compounds is complicated, but manageable because each compound is synthesized with the same set of chemical protocols, the difference being the random order in which amino acids or nucleotides are introduced into the reaction sequence.
The prior art Is replete with examples showing enzymatic conversion of non-physiological substances under many conditions.
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Taxol1, a diterpenold originally isolated from the bark of the Pacific yew, Taxus brevifolia, is a powerful antimitotic agent2 that acts by promoting tubulin assembly into stable aggregated structures. Taxol has shown tremendous potential as an anticancer compound. Indeed, it is now used for the treatment of refractory ovarian cancer3, and clinical trials are encouraging for the treatment of breast, lung4, head, and neck5 cancers. Because of its broad antitumor activity and limited availability, numerous studies have been devoted to the synthesis6 (including semisynthesis from the baccatin III nucleus7) , mechanism1, and structure-activity relationships of taxol and protaxols.1a,1d,8 Despite such intense investigation, the use of taxol as an anticancer drug is compromised by its poor aqueous solubility. For this reason, a number of water-soluble taxol prodrugs have been synthesized that contain hydrophilic or charged functionalities attached to specific sites on the taxol molecule.9 
Acylation at the 2xe2x80x2 position can be a very effective strategy for improving the water solubility of taxol.9a-e Interestingly, acylation of the C-2xe2x80x2 hydroxyl eliminates microtube stabilization but not cytotoxicity, which is consistent with the hydrolytic regeneration of taxol from protaxol within the cell.8 Water soluble protaxols modified at the 2xe2x80x2 position include arylsulfonyl ethoxycarbonates and thiodiglycolic esters synthesized by Nicolaou et al.9a, the most soluble of which were 100 to 1000 times more soluble than taxol.
Accordingly, taxol derivatives with improved solubiity are sought.
According to one embodiment of the present invention is taxol-2xe2x80x2-adipate derivatives.
According to another embodiment of the present invention is derivatives of bergenin.
According to another embodiment of the present invention is derivatives erythromycyin.
According to another embodiment of the present invention is a library of derivatives based on 2,3-(methylenedioxy)benzaldehyde.
According to another embodiment of the present invention is a library of derivatives based on (xc2x1)-(2-endo,3-exo)-bicyclo[2.2.2]octo-5-ene-2,3-dimethanol.
According to another embodiment of the present invention is a library of derivatives based on adenosine.
These and other objects of the present invention are made possible by the taxol-2xe2x80x2-adipate derivatives of the formula. 
wherein:
R1 is hydrogen, C1-10 alkyl ester, halosubstituted C1-10 alkyl ester, or CO(CH2)nCOR2 where n is an integer of 2-10 and R3 is hydrogen, C1-10 alkyl or C1-10 alkenyl;
n is an integer of 2-10; and
R2 is hydrogen, C1-10 alkyl, C1-10 alkenyl, or a 6 substituted saccharide compound selected from the group consisting of glucose, galactose, allose, altrose, mannose, gulose, idose, talose, lactose, cellobiose, sucrose, fructose and maltose, in the open or pyranose form.
These and other objects of the present invention are made possible by derivatives of bergenin, of the formula 
wherein
R4, R5, and R6 are each independently hydrogen, C1-10 alkyl ester, C1-10 alkyl substituted C1-10 alkyl ester, halosubstituted C1-10 alkyl ester, C6-20 aralkyl ester, halo substituted C6-20 aralkyl ester, C6-20 aralkenyl ester, a 1 substituted saccharide compound selected from the group consisting of glucose, galactose, allose, altrose, mannose, gulose, idose, talose, lactose, cellobiose, sucrose, fructose, deoxynojirimycin, N-acetyl glucoseamine, N-acetyl galactoseamine, and maltose, or CO(CH2)nCOR10 
where n is an integer of 2-10; and
R10 is OH, C1-10 alkoxy, C1-10 alkenyloxy, a 6 substituted saccharide compound selected from the group consisting of glucose, galactose, allose, altrose, mannose, gulose, idose, talose, lactose, cellobiose, sucrose, fructose and maltose, in the open or pyranose form, NR11R12 where R11 and R12 are each independently hydrogen, C1-10 alkyl, substitued C1-10 alkyl substitued with C1-10 alkyl, C6-20 aryl or halogen;
R7 is H, OH, F, Cl, Br, or I;
R8 and R9 are each independently hydrogen or C1-10 alkyl, provided that when R7 is H, R4, R5 and R6 are not each hydrogen.
These and other objects of the present invention are made possible by erythromycin derivatives of the formula 
wherein
R13 is hydrogen or OH;
R14 is CH3 or CO2H; and
R15 is hydrogen or CO(CH2)nCOR16 
where n is an integer of 2-10; and
R16 is OH, C1-10 alkoxy , C1-10 alkenyloxy, a 6 substituted saccharide compound selected from the group consisting of glucose, galactose, allose, altrose, mannose, gulose, idose, talose, lactose, cellobiose, sucrose, fructose and maltose, NR17R18 where R17 and R18 are each independently hydrogen, C1-10 alkyl, substitued C1-10 alkyl substitued with C1-10 alkyl, C6-20 aryl or halogen;
provided that when R13 and R15 are each hydrogen, R14 is not CH3.